Continuous Tracking for Effective Tackling: Ad5/35 Platform-Based JN1 Lineage Vaccines Development in Response to Evolving SARS-CoV-2 Variants.

The SARS-CoV-2 virus is continuously evolving, such that JN.1 and its subvariants, including KP.2, KP.3, and LB.1, are now predominant variants globally. JN.1 is derived from BA.2.86, which harbors more than 30 mutations in the spike protein compared with those of XBB and BA.2, and it carries an additional L455S mutation. Given the rapid evolution of these variants, assessing the neutralization capacity of current JN.1 lineage vaccines against prevalent variants, such as KP.3, is critical. Phylogenetic trees using spike protein sequences and antigenic cartography based on neutralization results reveal that JN.1 lineage variants are antigenically distant from previously circulating variants. Moreover, JN.1 subvariants showed inadequate neutralization titers compared with other variants against XBB.1.5-containing vaccine in mice. Immunization with vaccines targeting the JN.1, KP.2, KP.3, and LB.1 variants demonstrated significant neutralizing activity against predominant variants in mice. These results highlight the importance of vaccine development to keep pace with the evolution of SARS-CoV-2 variants and the need for updated vaccines targeting the JN.1 variant.